tbuckley/cabot-search huggingface dataset:
Safety and efficacy of CD22 and CD19 CAR-T bridging auto-HSCT as consolidation therapy for AYA and adult B-ALL
Authors: Yan Qiu, Chao-Ling Wan, Ming-Zhu Xu, Hai-Xia Zhou, Mei-Jing Liu, Wen-Jie Gong, Li-Qing Kang, Ai-Ning Sun, Lei Yu, De-Pei Wu, Chong-Sheng Qian, Sheng-Li Xue
Journal: Blood Cancer Journal (2023)
SARS-CoV-2 self-test uptake and factors associated with self-testing during Omicron BA.1 and BA.2 waves in France, January to May 2022
Authors: Olivier Supplisson, Tiffany Charmet, Simon Galmiche, Laura Schaeffer, Olivia Chény, Anne Lévy, Nathan Jeandet, Faïza Omar, Christophe David, Alexandra Mailles, Arnaud Fontanet
Journal: Eurosurveillance (2023)

BackgroundFollowing the SARS-CoV-2 Omicron variant spread, the use of unsupervised antigenic rapid diagnostic tests (self-tests) increased.AimThis study aimed to measure self-test uptake and factors associated with self-testing.MethodsIn this cross-sectional study from 20 January to 2 May 2022, the case series from a case-control study on factors associated with SARS-CoV-2 infection were used to analyse self-testing habits in France. A multivariable quasi-Poisson regression was used to explore the variables associated with self-testing among symptomatic cases who were not contacts of another infected individual. The control series from the same study was used as a proxy for the self-test background rate in the non-infected population of France.ResultsDuring the study period, 179,165 cases who tested positive through supervised tests were recruited. Of these, 64.7% had performed a self-test in the 3 days preceding this supervised test, of which 79,038 (68.2%) were positive. The most frequently reported reason for self-testing was the presence of symptoms (64.6%). Among symptomatic cases who were not aware of being contacts of another case, self-testing was positively associated with being female, higher education, household size, being a teacher and negatively associated with older age, not French by birth, healthcare-related work and immunosuppression. Among the control series, 12% self-tested during the 8 days preceding questionnaire filling, with temporal heterogeneity.ConclusionThe analysis showed high self-test uptake in France with some inequalities which must be addressed through education and facilitated access (cost and availability) for making it a more efficient epidemic control tool.
The role of children in transmission of SARS-CoV-2 variants of concern within households: an updated systematic review and meta-analysis, as at 30 June 2022
Authors: Yanshan Zhu, Yao Xia, Janessa Pickering, Asha C Bowen, Kirsty R Short
Journal: Eurosurveillance (2023)

Background Meta-analyses and single-site studies have established that children are less infectious than adults within a household when positive for ancestral SARS-CoV-2. In addition, children appear less susceptible to infection when exposed to ancestral SARS-CoV-2 within a household. The emergence of SARS-CoV-2 variants of concern (VOC) has been associated with an increased number of paediatric infections worldwide. However, the role of children in the household transmission of VOC, relative to the ancestral virus, remains unclear. Aim We aimed to evaluate children's role in household transmission of SARS-CoV-2 VOC. Methods We perform a meta-analysis of the role of children in household transmission of both ancestral SARS-CoV-2 and SARS-CoV-2 VOC. Results Unlike with the ancestral virus, children infected with VOC spread SARS-CoV-2 to an equivalent number of household contacts as infected adults and were equally as likely to acquire SARS-CoV-2 VOC from an infected family member. Interestingly, the same was observed when unvaccinated children exposed to VOC were compared with unvaccinated adults exposed to VOC. Conclusions These data suggest that the emergence of VOC was associated with a fundamental shift in the epidemiology of SARS-CoV-2. It is unlikely that this is solely the result of age-dependent differences in vaccination during the VOC period and may instead reflect virus evolution over the course of the pandemic.
Red-flag signs and symptoms for earlier diagnosis of early-onset colorectal cancer
Authors: Cassandra D L Fritz, Ebunoluwa E Otegbeye, Xiaoyu Zong, Joshua Demb, Katelin B Nickel, Margaret A Olsen, Matthew Mutch, Nicholas O Davidson, Samir Gupta, Yin Cao
Journal: JNCI Journal of the National Cancer Institute (2023)

Abstract Background Prompt detection of colorectal cancer (CRC) among individuals younger than age 50 years (early-onset CRC) is a clinical priority because of its alarming rise. Methods We conducted a matched case-control study of 5075 incident early-onset CRC among US commercial insurance beneficiaries (113 million adults aged 18-64 years) with 2 or more years of continuous enrollment (2006-2015) to identify red-flag signs and symptoms between 3 months to 2 years before the index date among 17 prespecified signs and symptoms. We assessed diagnostic intervals according to the presence of these signs and symptoms before and within 3 months of diagnosis. Results Between 3 months and 2 years before the index date, 4 red-flag signs and symptoms (abdominal pain, rectal bleeding, diarrhea, and iron deficiency anemia) were associated with an increased risk of early-onset CRC, with odds ratios (ORs) ranging from 1.34 to 5.13. Having 1, 2, or at least 3 of these signs and symptoms were associated with a 1.94-fold (95% confidence interval [CI] = 1.76 to 2.14), 3.59-fold (95% CI = 2.89 to 4.44), and 6.52-fold (95% CI = 3.78 to 11.23) risk (Ptrend &amp;lt; .001), respectively, with stronger associations for younger ages (Pinteraction &amp;lt; .001) and rectal cancer (Pheterogenity = .012). The number of different signs and symptoms was predictive of early-onset CRC beginning 18 months before diagnosis. Approximately 19.3% of patients had their first sign or symptom occur between 3 months and 2 years before diagnosis (median diagnostic interval = 8.7 months), and approximately 49.3% had the first sign or symptom within 3 months of diagnosis (median diagnostic interval = 0.53 month). Conclusions Early recognition of red-flag signs and symptoms (abdominal pain, rectal bleeding, diarrhea, and iron-deficiency anemia) may improve early detection and timely diagnosis of early-onset CRC.
Reporting of Immunotherapy and Biologic Therapy in the National Cancer Database—Reply
Authors: Sameh Hany Emile, Nir Horesh, Steven D. Wexner
Journal: JAMA Oncology (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Oncology HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2024 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Oncology journal
COVID-19 Mortality Update — United States, 2022
Authors: Farida B. Ahmad, Jodi A. Cisewski, Jiaquan Xu, Robert N. Anderson
Journal: MMWR Morbidity and Mortality Weekly Report (2023)

The National Center for Health Statistics' (NCHS) National Vital Statistics System (NVSS) collects and reports annual mortality statistics using U.S. death certificate data. Provisional data, which are based on the current flow of death certificate data to NCHS, provide an early estimate of deaths before the release of final data.* This report summarizes provisional U.S. COVID-19 death data for 2022. In 2022, COVID-19 was the underlying (primary) or contributing cause in the chain of events leading to 244,986 deaths† that occurred in the United States. During 2021-2022, the estimated age-adjusted COVID-19-associated death rate decreased 47%, from 115.6 to 61.3 per 100,000 persons. COVID-19 death rates were highest among persons aged ≥85 years, non-Hispanic American Indian or Alaska Native (AI/AN) populations, and males. In 76% of deaths with COVID-19 listed on the death certificate, COVID-19 was listed as the underlying cause of death. In the remaining 24% of COVID-19 deaths, COVID-19 was a contributing cause. As in 2020 and 2021, during 2022, the most common location of COVID-19 deaths was a hospital inpatient setting (59%). However, an increasing percentage occurred in the decedent's home (15%), or a nursing home or long-term care facility (14%).§ Provisional COVID-19 death estimates provide an early indication of shifts in mortality trends and can help guide public health policies and interventions aimed at reducing COVID-19-associated mortality.
An African-Specific Variant of<i>TP5</i>3 Reveals PADI4 as a Regulator of p53-Mediated Tumor Suppression
Authors: Alexandra Indeglia, Jessica C. Leung, Sven A. Miller, Julia I-Ju Leu, James F. Dougherty, Nicole L. Clarke, Nicole A. Kirven, Chunlei Shao, Lei Ke, Scott Lovell, Thibaut Barnoud, David Y. Lu, Cindy Lin, Toshitha Kannan, Kevin P. Battaile, Tyler Hong Loong Yang, Isabela Batista Oliva, Daniel T. Claiborne, Peter Vogel, Lijun Liu, Qin Liu, Yulia Nefedova, Joel Cassel, Noam Auslander, Andrew V. Kossenkov, John Karanicolas, Maureen E. Murphy
Journal: Cancer Discovery (2023)

Abstract TP53 is the most frequently mutated gene in cancer, yet key target genes for p53-mediated tumor suppression remain unidentified. Here, we characterize a rare, African-specific germline variant of TP53 in the DNA-binding domain Tyr107His (Y107H). Nuclear magnetic resonance and crystal structures reveal that Y107H is structurally similar to wild-type p53. Consistent with this, we find that Y107H can suppress tumor colony formation and is impaired for the transactivation of only a small subset of p53 target genes; this includes the epigenetic modifier PADI4, which deiminates arginine to the nonnatural amino acid citrulline. Surprisingly, we show that Y107H mice develop spontaneous cancers and metastases and that Y107H shows impaired tumor suppression in two other models. We show that PADI4 is itself tumor suppressive and that it requires an intact immune system for tumor suppression. We identify a p53–PADI4 gene signature that is predictive of survival and the efficacy of immune-checkpoint inhibitors. Significance: We analyze the African-centric Y107H hypomorphic variant and show that it confers increased cancer risk; we use Y107H in order to identify PADI4 as a key tumor-suppressive p53 target gene that contributes to an immune modulation signature and that is predictive of cancer survival and the success of immunotherapy. See related commentary by Bhatta and Cooks, p. 1518. This article is highlighted in the In This Issue feature, p. 1501
Evolutionary Trajectories of New Duplicated and Putative De Novo Genes
Authors: José Carlos Montañés, Marta Huertas, Xavier Messeguer, M Mar Albà
Journal: Molecular Biology and Evolution (2023)

Abstract The formation of new genes during evolution is an important motor of functional innovation, but the rate at which new genes originate and the likelihood that they persist over longer evolutionary periods are still poorly understood questions. Two important mechanisms by which new genes arise are gene duplication and de novo formation from a previously noncoding sequence. Does the mechanism of formation influence the evolutionary trajectories of the genes? Proteins arisen by gene duplication retain the sequence and structural properties of the parental protein, and thus they may be relatively stable. Instead, de novo originated proteins are often species specific and thought to be more evolutionary labile. Despite these differences, here we show that both types of genes share a number of similarities, including low sequence constraints in their initial evolutionary phases, high turnover rates at the species level, and comparable persistence rates in deeper branchers, in both yeast and flies. In addition, we show that putative de novo proteins have an excess of substitutions between charged amino acids compared with the neutral expectation, which is reflected in the rapid loss of their initial highly basic character. The study supports high evolutionary dynamics of different kinds of new genes at the species level, in sharp contrast with the stability observed at later stages.
CellMinerCDB: NCATS Is a Web-Based Portal Integrating Public Cancer Cell Line Databases for Pharmacogenomic Explorations
Authors: William C. Reinhold, Kelli Wilson, Fathi Elloumi, Katie R. Bradwell, Michele Ceribelli, Sudhir Varma, Yanghsin Wang, Damien Duveau, Nikhil Menon, Jane Trepel, Xiaohu Zhang, Carleen Klumpp-Thomas, Samuel Micheal, Paul Shinn, Augustin Luna, Craig Thomas, Yves Pommier
Journal: Cancer Research (2023)

Major advances have been made in the field of precision medicine for treating cancer. However, many open questions remain that need to be answered to realize the goal of matching every patient with cancer to the most efficacious therapy. To facilitate these efforts, we have developed CellMinerCDB: National Center for Advancing Translational Sciences (NCATS; https://discover.nci.nih.gov/rsconnect/cellminercdb_ncats/), which makes available activity information for 2,675 drugs and compounds, including multiple nononcology drugs and 1,866 drugs and compounds unique to the NCATS. CellMinerCDB: NCATS comprises 183 cancer cell lines, with 72 unique to NCATS, including some from previously understudied tissues of origin. Multiple forms of data from different institutes are integrated, including single and combination drug activity, DNA copy number, methylation and mutation, transcriptome, protein levels, histone acetylation and methylation, metabolites, CRISPR, and miscellaneous signatures. Curation of cell lines and drug names enables cross-database (CDB) analyses. Comparison of the datasets is made possible by the overlap between cell lines and drugs across databases. Multiple univariate and multivariate analysis tools are built-in, including linear regression and LASSO. Examples have been presented here for the clinical topoisomerase I (TOP1) inhibitors topotecan and irinotecan/SN-38. This web application provides both substantial new data and significant pharmacogenomic integration, allowing exploration of interrelationships.CellMinerCDB: NCATS provides activity information for 2,675 drugs in 183 cancer cell lines and analysis tools to facilitate pharmacogenomic research and to identify determinants of response.
Racial and Ethnic Differences in Insurer Classification of Nonemergent Pediatric Emergency Department Visits
Authors: Alexander Pomerantz, Heidi G. De Souza, Matthew Hall, Mark I. Neuman, Monika K. Goyal, Margaret E. Samuels-Kalow, Paul L. Aronson, Elizabeth R. Alpern, Harold K. Simon, Jennifer A. Hoffmann, Jordee M. Wells, Kristen H. Shanahan, Colleen K. Gutman, Alon Peltz
Journal: JAMA Network Open (2023)

Importance Government and commercial health insurers have recently enacted policies to discourage nonemergent emergency department (ED) visits by reducing or denying claims for such visits using retrospective claims algorithms. Low-income Black and Hispanic pediatric patients often experience worse access to primary care services necessary for preventing some ED visits, raising concerns about the uneven impact of these policies. Objective To estimate potential racial and ethnic disparities in outcomes of Medicaid policies for reducing ED professional reimbursement based on a retrospective diagnosis-based claims algorithm. Design, Setting, and Participants This simulation study used a retrospective cohort of pediatric ED visits (aged 0-18 years) for Medicaid-insured children and adolescents appearing in the Market Scan Medicaid database between January 1, 2016, and December 31, 2019. Visits missing date of birth, race and ethnicity, professional claims data, and Current Procedural Terminology codes of billing level of complexity were excluded, as were visits that result in admission. Data were analyzed from October 2021 to June 2022. Main Outcomes and Measures Proportion of ED visits algorithmically classified as nonemergent and simulated per-visit professional reimbursement after applying a current reimbursement reduction policy for potentially nonemergent ED visits. Rates were calculated overall and compared by race and ethnicity. Results The sample included 8 471 386 unique ED visits (43.0% by patients aged 4-12 years; 39.6% Black, 7.7% Hispanic, and 48.7% White), of which 47.7% were algorithmically identified as potentially nonemergent and subject to reimbursement reduction, resulting in a 37% reduction in ED professional reimbursement across the study cohort. More visits by Black (50.3%) and Hispanic (49.0%) children were algorithmically identified as nonemergent when compared with visits by White children (45.3%; P &amp;amp;lt; .001). Modeling the impact of the reimbursement reductions across the cohort resulted in expected per-visit reimbursement that was 6% lower for visits by Black children and 3% lower for visits by Hispanic children relative to visits by White children. Conclusions and Relevance In this simulation study of over 8 million unique ED visits, algorithmic approaches for classifying pediatric ED visits that used diagnosis codes identified proportionately more visits by Black and Hispanic children as nonemergent. Insurers applying financial adjustments based on these algorithmic outputs risk creating uneven reimbursement policies across racial and ethnic groups.
Tick-borne encephalitis epidemiology and surveillance in Poland, and comparison with selected European countries before and during the COVID-19 pandemic, 2008 to 2020
Authors: Iwona Paradowska-Stankiewicz, Katarzyna Pancer, Anna Poznańska, Martyna Hordowicz, Maria Skibicka, Marek Słowiński, Gerard Motak, Bogdan Falkiewicz
Journal: Eurosurveillance (2023)

BackgroundTick-borne encephalitis (TBE) is the most common viral central nervous system (CNS) infection in Poland. Previous research suggests that its incidence was underestimated in the pre-pandemic period. The COVID-19 pandemic caused a considerable burden on surveillance systems, which could further impact reporting.AimWe aimed to assess the completeness of reporting of TBE in the years 2008 to 2020 and explore the potential impact of the COVID-19 pandemic on reporting to the epidemiological surveillance system, compared with hospitalisations for TBEV and other viral neuro-infections.MethodsWe compared the Polish epidemiology of TBE and other viral infections of the CNS from national surveillance reports with data on hospitalisations from 2008 to 2020 and data from selected European countries.ResultsBetween 2008 and 2020, 3,016 TBE cases were reported to surveillance compared with 3,620 hospitalisations. There was an increasing trend in hospitalisations, while surveillance data demonstrated the opposite, with the largest discrepancy observed in the first pandemic year (354 hospitalisations vs 159 cases reported to surveillance). Serological testing for TBE was used more in the known endemic region of north-eastern Poland and less in non-endemic areas. Other European countries reported higher TBE case numbers and an increase during the COVID-19 pandemic, whereas Poland observed an opposite trend.ConclusionThe sensitivity of TBE surveillance in Poland requires improvement. There are considerable regional differences. Regions that test for TBE intensively report most cases. Policymakers should be made aware of the value of quality epidemiological data for planning prophylactic measures in risk areas.
Basement membrane proteins in extracellular matrix characterize NF1 neurofibroma development and response to MEK inhibitor
Authors: Chunhui Jiang, Ashwani Kumar, Ze Yu, Tracey Shipman, Yong Wang, Renee M. McKay, Chao Xing, Lu Q. Le
Journal: Journal of Clinical Investigation (2023)

Neurofibromatosis type 1 (NF1) is one of the most common tumor-predisposing genetic disorders. Neurofibromas are NF1-associated benign tumors. A hallmark feature of neurofibromas is an abundant collagen-rich extracellular matrix (ECM) that constitutes more than 50% of the tumor dry weight. However, little is known about the mechanism underlying ECM deposition during neurofibroma development and treatment response. We performed a systematic investigation of ECM enrichment during plexiform neurofibroma (pNF) development and identified basement membrane (BM) proteins, rather than major collagen isoforms, as the most upregulated ECM component. Following MEK inhibitor treatment, the ECM profile displayed an overall downregulation signature, suggesting ECM reduction as a therapeutic benefit of MEK inhibition. Through these proteomic studies, TGF-β1 signaling was identified as playing a role in ECM dynamics. Indeed, TGF-β1 overexpression promoted pNF progression in vivo. Furthermore, by integrating single-cell RNA sequencing, we found that immune cells including macrophages and T cells produce TGF-β1 to induce Schwann cells to produce and deposit BM proteins for ECM remodeling. Following Nf1 loss, neoplastic Schwann cells further increased BM protein deposition in response to TGF-β1. Our data delineate the regulation governing ECM dynamics in pNF and suggest that BM proteins could serve as biomarkers for disease diagnosis and treatment response.